A Research Study Investigating Semaglutide in People With Early Alzheimer's Disease (EVOKE Plus)

Summary

This study is done to find out whether the medicine, semaglutide, has a positive effect on early Alzheimer's disease. Participants will either get semaglutide or placebo (a "dummy" medicine which does not contain any study medicine) - which treatment participants get is decided by an equal chance. The study will last for up to 173 weeks (about 3 years and 4 months). Participants will have 17 clinic visits and 1 phone call with the study doctor. The study includes various tests and scans. At 10 of the clinic visits participants will have blood samples taken. Participants must have a study partner, who is willing to take part in the study. Women cannot take part if pregnant, breastfeeding or plan to become pregnant during the study period. A cerebrospinal fluid (CSF) sub-study will be performed as a part of the study. The sub-study will be performed on a selection of sites based on their experience with CSF sampling and willingness to participate in this sub-study. The endpoints related to this sub-study are exploratory only.

Timeline

Start

2021-05-18

Primary completion

2025-09-15

Completion

2026-01-30

Publications

• Cummings JL, Atri A, Sano M, Zetterberg H, Scheltens P, Knop FK, Johannsen P, Wichmann CA, Abschneider RM, Leon T, Feldman HH. Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials. Lancet. 2026 May 30;407(10544):2167-2179. doi: 10.1016/S0140-6736(26)00459-9. Epub 2026 Mar 19.
• Scheltens P, Atri A, Feldman HH, Zetterberg H, Sano M, Johannsen P, Colombo TL, Bardtrum L, Jeppesen R, Hansen CT, Cummings JL. Baseline characteristics from evoke and evoke+: Two phase 3 randomized placebo-controlled trials of semaglutide in participants with early-stage symptomatic Alzheimer's disease. Alzheimers Dement (N Y). 2026 Jan 10;12(1):e70200. doi: 10.1002/trc2.70200. eCollection 2026 Jan-Mar.
• Cummings JL, Atri A, Feldman HH, Hansson O, Sano M, Knop FK, Johannsen P, Leon T, Scheltens P. evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease. Alzheimers Res Ther. 2025 Jan 8;17(1):14. doi: 10.1186/s13195-024-01666-7.
• van Sloten TT, Luchsinger JA, Launer LJ, Strachan M, Cukierman-Yaffe T, Gerstein HC, Sattar N, Biessels GJ. Call for effective therapies for preventing dementia in people with type 2 diabetes. Lancet Diabetes Endocrinol. 2024 Aug;12(8):510-513. doi: 10.1016/S2213-8587(24)00158-X. Epub 2024 Jun 17. No abstract available.

Drugs

Indications